Recently it has been reported that 1,4,5,7-tetrahydrofuro[3,4-b]pyridine compounds which may be represented by the formula ##STR1## have physiological properties which are antithetical to those possessed by ##STR2## which have been studied extensively as calcium slow channel blocking drugs. GB Pat. No. 2,105,989A, U.S. Pat. No. 4,284,634 and H. Meyer et al, Arzneim-Forsch/Drug Research 33(I) Nr 1 (1983), p. 106 teach various dihydropyridines including the foregoing 1,4,5,7-tetrahydrofuro[3,4-b]pyridine compounds to have useful properties of increasing the influx of calcium ion into cells and to be adaptable for use in combating coronary and vascular diseases. The 1,4,5,7-tetrahydrofuro[3,4-b]pyridine compounds have been prepared by condensing a protected 4-hydroxyacetoacetic ester with methyl .beta.-aminocrotonate and an appropriate aldehyde and the resulting dihydropyridine compound heated with alkali to remove the protecting group and to effect cyclization. The process is cumbersome, especially since the 4-hydroxyacetoacetic ester is not readily available and the preparation of the protected 4-hydroxyacetoacetic ester is a multistep procedure. It is desirable to provide for a facile synthesis of 1,4,5,7-tetrahydrofuro[3,4-b]pyridine compounds for studies directed to mechanism of drug action and for ultimate development of superior agents for the treatment of cardiovascular diseases.
Although bromine has been reported to react with 5-carbethoxy-6-methyldihydropyrimidine-2-one to form a bromomethyl compound which could be caused to cyclize on heating with phenol or aqueous ethanol, G. Zigeuner et al., Monatshefte fur Chemie, 97, 1408 (1966), no useful bromomethyl compound was obtained by reacting bromine with the non-analogous dihydropyridine compounds and 1,4,5,7-tetrahydrofuro[3,4-b]-pyridine compounds could not be satisfactorily produced. Thus, a good synthetic method, particularly from readily available starting materials is highly desirable.